Luteolin suppresses the JAK/STAT pathway in a cellular model of intestinal inflammation

Abstract

Current treatment strategies for inflammatory bowel diseases (IBDs) are associated with a lower efficacy and with several side effects that strongly affect the quality of life of IBD patients. Consequently, the development of new therapies, combining efficacy and safety is an important goal in the field of intestinal inflammation. In this context, evidence supports that polyphenols can be promising candidates due to their ability to modulate intracellular inflammatory signalling cascades. Luteolin, a naturally occurring flavonoid, exhibits anti-inflammatory properties in several models of inflammation. However, its action against intestinal inflammation has been poorly explored. Therefore, there is a lack of scientific knowledge about the potential impact of luteolin in the intestinal inflammation, particularly regarding the underlying molecular mechanisms by which luteolin can exert its anti-inflammatory action. We assessed the potential anti-inflammatory effect of luteolin in a cellular model of intestinal inflammation using cytokine-stimulated HT-29 colon epithelial cells, and the underlying key molecular mechanisms were identified. Luteolin significantly inhibited interleukine-8 (IL-8) production, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression and nitric oxide (˙NO) overproduction induced by cytokines, indicating that luteolin negatively modulates key inflammatory signalling cascades underlying intestinal inflammation. Mechanistically, the inhibition of the JAK/STAT pathway was identified as a critical mechanism by which luteolin exerts its intestinal anti-inflammatory action. This study uncovers novel molecular mechanisms by which luteolin may act against intestinal inflammation, which might support the use of luteolin as a future therapeutic strategy in IBD.

Human Heme Oxygenase-1 Induced by Interleukin-6 via JAK/STAT3 Pathways Is a Tumor Suppressor Gene in Hepatoma Cells

“…The results agree with a previous study in human multiple myeloma cells [23]. Luteolin, a natural flavonoid with potent anti-inflammatory properties, has believed to be able to block the JAK/STAT pathway [56]. After luteolin treatment, IL-6 affected either STAT3 phosphorylation or HO-1 expression was inhibited ( Figure 7B).…”

Kaempferol inhibits multiple pathways involved in the secretion of inflammatory mediators from LPS‑induced rat intestinal microvascular endothelial cells

“…It is well documented that the STAT pathway is not only associated with the inflammatory process in IBD; however, is additionally associated with further serious conditions, including colorectal cancer development (38,39). Recent studies demonstrated that luteolin, a naturally occurring flavonoid, inhibited the Janus kinase (JAK)/STAT pathway in cytokine-induced HT-29 cells, a human epithelial cell line (39). Curcumin, a natural phenol, suppressed inflammation of TNBS-induced colitis in mice via STAT signaling (40).…”

Anti-inflammatory effects of Nelumbo leaf extracts and identification of their metabolites

“…Moreover, taxifolin glycoside significantly reduced atopic dermatitis by effects on iNOS and COX-2 [ 35 ] and also ameliorated cerebral ischemia-reperfusion injury by inhibiting NF-κB activity [ 38 ]. However, NLEE contains luteolin which suppressed inflammation in several model through JAK/STAT and/or NF-κB pathway [ 39 40 41 ]. Luteolin reduced iNOS expression through inhibition of NF-κB translocation in LPSstimulated RAW 264.7 cells [ 39 ].…”